Structure of 23156-27-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 23156-27-6 |
Formula : | C6H4F2N2O2 |
M.W : | 174.11 |
SMILES Code : | NC1=C(F)C=C(C=C1F)[N+]([O-])=O |
MDL No. : | MFCD03094274 |
InChI Key : | WDFFWUVELIFAOP-UHFFFAOYSA-N |
Pubchem ID : | 2774175 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 39.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.01 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.3 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.14 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.12 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.02 |
Solubility | 1.65 mg/ml ; 0.00947 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.38 |
Solubility | 0.73 mg/ml ; 0.00419 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.97 |
Solubility | 1.85 mg/ml ; 0.0106 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.46 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
3.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.9 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The 3,5-difluoro-4-cyanophenol can be obtained by nitrating 2,6-difluoroaniline, diazotizing the resulting 4-nitro-2,6-difluoroaniline, decomposing the diazonium salt in the presence of a cuprous cyanide to obtain 4-nitro-2,6-difluoro-1-cyanobenzene, reducing the product to obtain 4-cyano-3,5-difluoroaniline, and decomposing its diazonium salt in sulfuric acid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | A suspension of 3-[4-(1 ,3-benzoxazol-2-yl)piperazin-1 -yl]propyl-N-(2,6-difluoro-4-nitro- phenyl)carbamate (125 mg, 0.271 mmol) and 10% Pd/C (125 mg) in DCM (2.5 mL) and EtOH (2.5 mL) was hydrogenated at room temperature for 4 days. The mixture was filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford compound 7 3-[4-(1 ,3-benzoxazol-2-yl)piperazin-1 - yl]propyl-N-(2,6-difluoro-4-amino-phenyl)carbamate (4.4 mg, 3.7%). ESI-MS m/z: 432 ([M+H]+) 100%); RT =9.38 min (Method 2B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | A solution of triphosgene (127 mg, 0.43mmol, 0.5 eq.) and <strong>[23156-27-6]2,6-difluoro-4-nitroaniline</strong> (347 mg, 0.86 mmol, 1 eq.) in dry DCM (5 mL) was stirred at 0 <C under an inert atmosphere for 1 hour. After a solution of triethylamine (0.48 mL, 3.44 mmol, 4 eq.) in dry DCM (4 mL) was added, the mixture was stirred at room temperature for 1 hour before a solution of 1 -[4-(1 ,3-benzothiazol-2-yl)piperazin-1 -yl]-3-hydroxy-propan-1 -one (250 mg, 0.86mmol, 1 eq.) in dry DCM (5 mL) was added . The reaction was stirred at room temperature for 20 hours before water (10 mL) was added. The mixture was extracted with ethyl acetate (3X15 mL) and the combined organic phases were dried over MgS04and concentrated under reduced pressure. The residue was purified by preparative flash silica chromatography (from ethyl acetate : hexane = 50 : 50 till 100% ethyl acetate) to afford [3-[4-(1 ,3-benzothiazol-2-yl)piperazin-1 -yl]-3-oxo-propyl] N-(4- nitro-2,6-difluoro-phenyl)carbamate (150 mg, 35%). ESI-MS m/z: 492 ([M+H]+), 100%); RT= 5.08 min (Method 4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | A solution of triphosgene (1 18 mg, 0.40 mmol, 0.75 eq.) and <strong>[23156-27-6]2,6-difluoro-4-nitroaniline</strong> (140 mg, 0.81 mmol, 1 .5 eq.) in dry DCM (10 mL) was stirred at 0C under an inert atmosphere for 15 min and then allowed to warm up to room temperature. After a solution of triethylamine (0.25 mL) was added, the mixture was stirred at room temperature for 1 hour before a solution of 3-[1 -(1 ,3-benzothiazol-2-yl)-4- piperidyl]propan-1 -ol (149 mg, 0.54 mmol, 1 eq.) in dry DCM (10 mL) and dry THF (10 mL) was added . The reaction was stirred at room temperature for 12 h before water (20 mL) was added. The mixture was extracted with ethyl acetate (3X20 mL) and the combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford 3-[4-(1 ,3- benzothiazol-2-yl)piperidyl]propyl-N-(2,6-difluoro-4-nitro-phenyl)carbamate (41 mg, 16%). ESI-MS m/z: 277 ([M+H]+) 100%) ; RT = 5.83 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With ammonia; In methanol; at 80℃; for 48h; | A solution of 3, 4, 5-trifluoro-1 -nitrobenzene (5 g, 28.4 mmol) in a 7N ammonia methanolic solution (30 mL) was stirred at 80 ^ for 2 days. After the mixture was allowed to cool down, water (50 mL) was added and the washed with ethyl acetate (3X100 mL). The organic phases were combined and washed with water (2X50 mL), dried over MgS04 and concentrated under reduced pressure. The product was purified by flash silica chromatography (ethyl acetate : hexane = 20 : 80) to afford 2,6-difluoro- 4-nitroaniline (1 .53 g, 31 %). ESI-MS m/z: 196 ([M+Na]+ , 100%); H NMR (600 MHz, DMSO-d6) delta ppm: 7.82-7-95 (m, 2 H), 6.86 (s, 2 H). |